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. 2023 Jun 12;13:9515. doi: 10.1038/s41598-023-36245-7

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Female mice display two types of formalin-induced pain behaviors, respectively marked by short- and long-lasting interphases. (a) Cumulative duration (left) and the duration per 5 min intervals (time-course, right) of formalin-evoked pain behavior (in seconds, s) in a small cohort of n = 8 male and n = 8 female mice. Data are presented as mean ± SEM. (*p < 0.05; **p < 0.01). (b) Individual data for the time-course of formalin-evoked pain in the females included the (a). (c) Cumulative duration (left) and time-course (right) of formalin-evoked nocifensive behavior (in seconds, s) in a large group of mice (n = 24 males and 53 females). Data are presented as mean ± SEM. (*p < 0.05). (d) K-means based subdivision of males and females; shows the percentage of subjects in each sub-group (males and outlier males and F1 and F2 females). (e) Cumulative duration (left) and time-course (right) of formalin-evoked nocifensive behavior (in seconds, s) in F1 (n = 29) and F2 (n = 24) females and in males (n = 24). Data are presented as mean ± SEM. (M-F1: ^$p < 0.05; ^$$$p < 0.001) (M-F2: ^øp < 0.05; ^øøp < 0.01) (F1-F2: *p < 0.05; ***p < 0.001). (f) Duration of the interphase in males (n = 24), F1 (n = 29) and F2 (n = 24) females (in minutes, min). Data are presented as mean ± SEM. (M-F1: ^$$$p < 0.001) (M-F2: ^øp < 0.05) (F1-F2: ***p < 0.001).